The hosts took control from the first whistle and Rickie Lambert came close to an early goal when he drilled a loose ball just wide of the target from inside the box.
Steven Gerrard made sure the home supporters didn't have to wait too long for an opening goal as the Liverpool midfielder collected a pass from Frank Lampard before firing the ball into the bottom corner.
England proved to be too strong for their opponents in every area and their dominance in midfield was obvious when Jack Wilshere danced through the visiting defence before striking his effort straight at Stanislav Namasco.
Lambert managed to make up for his earlier miss in the 26th minute to head home from close range after Namasco had failed to clear Theo Walcott's shot.
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Danny Welbeck received a booking just before half time to rule him out of next week's clash with Ukraine but the Manchester United forward managed to move past the disappointment quickly as he handed his side their third goal with an easy finish following poor football from Namasco.
England started the second half confidently as they did the first, with Lambert providing a perfect pass for Welbeck to chip in his second of the match.
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Moldova could barely get out of their own half for most of the match and England's defence were rarely threatened on a routine night in the capital.
England could have added more goals but Lampard was denied by Namasco before substitute James Milner missed a great chance from close range in injury time as the hosts eased to three points.